-chalcones obtained one-pot synthesis as the anti-neurodegenerative agents and their effect on the HT-22 cell line.

In the area of research on neurodegenerative diseases, the current challenge is to search for appropriate research methods that would detect these diseases at the earliest possible stage, but also new active structures that would reduce the rate of the disease progression and minimize the intensity of their symptoms experienced by the patient. The chalcones are considered in the context of candidates for new drugs dedicated to the fight against neurodegenerative diseases. The synthesis of -chalcone derivatives as aim molecules was performed. Their structures were established by applying H NMR, C NMR, MS, FT-IR and UV-Vis spectra. All -chalcones were synthesized from terephthalaldehyde and appropriate aromatic ketone as substrates in the Claisen-Schmidt condensation method and evaluated in the biological tests and analysis. Compounds exerted antioxidant activity using the HORAC method () and decreased the activities of GPx, COX-2 () GR () and CAT (. The high anti-neurodegenerative potential of all four chalcones was observed by inhibition of acetyl- (AChE) and butyrylcholinesterase (BChE) and a positive effect on the mouse hippocampal neuronal HT-22 cell line (LDH release and PGC-1α, PPARγ and GAPDH protein expression). TD-DFT method (computing a number of descriptors associated with HOMO-LUMO electron transition: electronegativity, chemical hardness and potential, first ionization potential, electron affinity) was employed to study the spectroscopic properties. This method showed that the first excited state of compounds was consistent with their maximum absorption in the computed UV-Vis spectra, which showed good agreement with the experimental spectrum using PBE1PBE functional. Using approach, interactions of -chalcones with selected targets (aryl hydrocarbon receptor (AhR) PAS-A Domain, ligand binding domain of human PPAR-γ, soman-aged human BChE-butyrylthiocholine complex, AChE:N-piperidinopropyl-galanthamine complex and the COX-2-celecoxib complex) were characterized. Results obtained in models were consistent with experiments.